tbuckley/cabot-search huggingface dataset:
Recent Use of Non–Vitamin K Antagonist Oral Anticoagulants and Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase
Authors: Jennifer A. Frontera, Tania Ahuja
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Retrospective Cohort Study of Treatment Outcomes of Adult Patients With Relapsed or Refractory Follicular Lymphoma (ReCORD-FL)
Authors: Gilles Salles, Stephen J. Schuster, Luca Fischer, John Kuruvilla, Piers E. M. Patten, Bastian von Tresckow, Sonali Smith, Ana Jiménez-Ubieto, Keith L. Davis, Saurabh Nagar, Jie Zhang, Vamsi Bollu, Etienne Jousseaume, Roberto Ramos, Yucai Wang, Brian K. Link
Journal: HemaSphere (2022)

This study (ReCORD-FL) sought to construct a historical control cohort to augment single-arm trials in relapsed/refractory follicular lymphoma (r/r FL). A retrospective study in 10 centers across North America and Europe was conducted. Adults with grade 1–3A FL were required to be r/r after ≥2 therapy lines including an anti-CD20 and an alkylator. After first becoming r/r, patients were required to initiate ≥1 additional therapy line, which defined the study index date. Endpoints were observed from start of each therapy line (including index line) until death, last follow-up, or December 31, 2020. Endpoints were complete response (CR) rate, overall response rate (ORR), time to next treatment or death (TNT-D), event-free survival (EFS), and overall survival (OS). One hundred eighty-seven patients were identified. Most patients’ (80.2%) index therapy occurred in third line (3L) (range, 3L–6L). Median follow-up from FL diagnosis was 9 years (range, 1–21 years). CR and ORR to the index therapy were 39.0% and 70.6%, respectively. Median (95% confidence interval) EFS from index was 14.6 (11.0-18.0) months; median OS from index was 10.6 years. Outcomes worsened across successive treatment lines and for patients who were double refractory (r/r to both an anti-CD20 monoclonal antibody and an alkylator) or POD24 (progressed ≤24 months after front-line anti-CD20) at index. Findings demonstrate the unmet need of FL patients with multiply relapsed, double refractory, or POD24 disease. Based on robustness of the historical data collected and comparability with a previous study (SCHOLAR-5), ReCORD-FL presents a valuable source of control data for comparative studies in r/r FL.
Oct4A palmitoylation modulates tumorigenicity and stemness in human glioblastoma cells
Authors: Xueran Chen, Wanxiang Niu, Xiaoqing Fan, Haoran Yang, Chenggang Zhao, Junqi Fan, Xuebiao Yao, Zhiyou Fang
Journal: Neuro-Oncology (2022)

Glioblastoma multiforme and other solid malignancies are heterogeneous, containing subpopulations of tumor cells that exhibit stem characteristics. Oct4, also known as POU5F1, is a key transcription factor in the self-renewal, proliferation, and differentiation of stem cells. Although it has been detected in advanced gliomas, the biological function of Oct4, and transcriptional machinery maintained by the stemness of Oct4 protein-mediated glioma stem cells (GSC), has not been fully determined.The expression of Oct4 variants was evaluated in brain cancer cell lines, and in brain tumor tissues, by quantitative real-time PCR, western blotting, and immunohistochemical analysis. The palmitoylation level of Oct4A was determined by the acyl-biotin exchange method, and the effects of palmitoylation Oct4A on GSCs were investigated by a series of in vitro (neuro-sphere formation assay, double immunofluorescence, pharmacological treatment, luciferase assay, and coimmunoprecipitation) and in vivo (xenograft model) experiments.Here, we report that all three variants of Oct4 are expressed in different types of cerebral cancer, while Oct4A is important for maintaining tumorigenicity in GSCs. Palmitoylation mediated by ZDHHC17 was indispensable for preserving Oct4A from lysosome degradation to maintain its protein stability. Oct4A palmitoylation also helped to integrate Sox4 and Oct4A in the SOX2 enhancement subregion to maintain the stem performance of GSCs. We also designed Oct4A palmitoylation competitive inhibitors, inhibiting the self-renewal ability and tumorigenicity of GSCs.These findings indicate that Oct4A acts on the tumorigenic activity of glioblastoma, and Oct4A palmitoylation is a candidate therapeutic target.
n-3 PUFA dietary lipid replacement normalizes muscle mitochondrial function and oxidative stress through enhanced tissue mitophagy and protects from muscle wasting in experimental kidney disease
Authors: Gianluca Gortan Cappellari, Annamaria Semolic, Giulia Ruozi, Davide Barbetta, Francesca Bortolotti, Pierandrea Vinci, Michela Zanetti, Robert H. Mak, Giacomo Garibotto, Mauro Giacca, Rocco Barazzoni
Journal: Metabolism (2022)
Initiation of ventricular arrhythmia in the acquired long QT syndrome
Authors: Cherry Alexander, Martin J Bishop, Rebecca J Gilchrist, Francis L Burton, Godfrey L Smith, Rachel C Myles
Journal: Cardiovascular Research (2022)

Abstract Aims Long QT syndrome (LQTS) carries a risk of life-threatening polymorphic ventricular tachycardia (Torsades de Pointes, TdP) and is a major cause of premature sudden cardiac death. TdP is induced by R-on-T premature ventricular complexes (PVCs), thought to be generated by cellular early-afterdepolarisations (EADs). However, EADs in tissue require cellular synchronisation, and their role in TdP induction remains unclear. We aimed to determine the mechanism of TdP induction in rabbit hearts with acquired LQTS (aLQTS). Methods and results Optical mapping of action potentials (APs) and intracellular Ca2+ was performed in Langendorff-perfused rabbit hearts (n = 17). TdP induced by R-on-T PVCs was observed during aLQTS (50% K+/Mg++ &amp; E4031) conditions in all hearts (P &amp;lt; 0.0001 vs. control). Islands of AP prolongation bounded by steep voltage gradients (VGs) were consistently observed before arrhythmia and peak VGs were more closely related to the PVC upstroke than EADs, both temporally (7 ± 5 ms vs. 44 ± 27 ms, P &amp;lt; 0.0001) and spatially (1.0 ± 0.7 vs. 3.6 ± 0.9 mm, P &amp;lt; 0.0001). PVCs were initiated at estimated voltages of ∼ −40 mV and had upstroke dF/dtmax and Vm-Ca2+ dynamics compatible with ICaL activation. Computational simulations demonstrated that PVCs could arise directly from VGs, through electrotonic triggering of ICaL. In experiments and the model, sub-maximal L-type Ca2+ channel (LTCC) block (200 nM nifedipine and 90% gCaL, respectively) abolished both PVCs and TdP in the continued presence of aLQTS. Conclusion These data demonstrate that ICaL activation at sites displaying steep VGs generates the PVCs which induce TdP, providing a mechanism and rationale for LTCC blockers as a novel therapeutic approach in LQTS.
Imaging strategies used in emergency departments for the diagnostic workup of COVID-19 patients during the first wave of the pandemic: a cost-effectiveness analysis
Authors: Sabrina Kepka, Kevin Zarca, Damien Viglino, Nicolas Marjanovic, Omide Taheri, Olivier Peyrony, Thibaut Desmettre, Valérie Wilme, Tania Marx, Joris Muller, Sebastien Harscoat, Pierrick Le Borgne, Eric Bayle, Nicolas Lefebvre, Yves Hansmann, Samira Fafi-Kremer, Mickaël Ohana, Isabelle Durand Zaleski, Pascal Bilbault
Journal: Clinical Microbiology and Infection (2022)
circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis
Authors: Liyuan Yu, Kai Xia, Jing Zhou, Zhiai Hu, Xing Yin, Chenchen Zhou, Shujuan Zou, Jun Liu
Journal: International Journal of Oral Science (2022)

Abstract Human adipose-derived stem cells (hASCs) are a promising cell type for bone tissue regeneration. Circular RNAs (circRNAs) have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis. However, how circRNAs regulate hASCs in osteogenesis is still unclear. Herein, we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs. Knockdown of circ_0003204 by siRNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs. We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p. We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 mRNA. The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis. Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model, while overexpression of circ_0003204 inhibited bone defect repair. Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.
Preoperative Atrial Fibrillation and Cardiovascular Outcomes After Noncardiac Surgery
Authors: Sameer Prasada, Milind Y. Desai, Marwan Saad, Nathaniel R. Smilowitz, Michael Faulx, Venu Menon, Rohit Moudgil, Pulkit Chaudhury, Ayman A. Hussein, Tyler Taigen, Shady Nakhla, Amgad Mentias
Journal: Journal of the American College of Cardiology (2022)
Re: Caelán Max Haney, Maximilian C. Kriegmair, Maurice Stephan Michel, Jens-Uwe Stolzenburg, Karl-Friedrich Kowalewski. New Evidence and Innovative Approaches to Blinding in Robot-assisted Radical Cystectomy. Eur Urol. 2022;81:615–617
Authors: Fabrizio Di Maida, Alessandro Larcher, Paolo Dell'Oglio, Andrea Minervini
Journal: European Urology (2022)
New Guidelines for Bronchodilator Responsiveness in COPD: A Test in Search of a Use
Authors: Surya P. Bhatt, Spyridon Fortis, Sandeep Bodduluri
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"New Guidelines for Bronchodilator Responsiveness in COPD: A Test in Search of a Use." American Journal of Respiratory and Critical Care Medicine, 206(8), pp. 1042–1044
Management of Metastatic Clear Cell Renal Cell Carcinoma: ASCO Guideline
Authors: W. Kimryn Rathmell, R. Bryan Rumble, Peter J. Van Veldhuizen, Hikmat Al-Ahmadie, Hamid Emamekhoo, Ralph J. Hauke, Alexander V. Louie, Matthew I. Milowsky, Ana M. Molina, Tracy L. Rose, Shankar Siva, Nicholas G. Zaorsky, Tian Zhang, Rubina Qamar, Terry M. Kungel, Bryan Lewis, Eric A. Singer
Journal: Journal of Clinical Oncology (2022)

To provide recommendations for the management of patients with metastatic clear cell renal cell carcinoma (ccRCC).An Expert Panel conducted a systematic literature review to obtain evidence to guide treatment recommendations.The panel considered peer-reviewed reports published in English.The diagnosis of metastatic ccRCC should be made using tissue biopsy of the primary tumor or a metastatic site with the inclusion of markers and/or stains to support the diagnosis. The International Metastatic RCC Database Consortium risk criteria should be used to inform treatment. Cytoreductive nephrectomy may be offered to select patients with kidney-in-place and favorable- or intermediate-risk disease. For those who have already had a nephrectomy, an initial period of active surveillance may be offered if they are asymptomatic with a low burden of disease. Patients with favorable-risk disease who need systemic therapy may be offered an immune checkpoint inhibitor (ICI) in combination with a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI); patients with intermediate or poor risk should be offered a doublet regimen (no recommendation was provided between ICIs or an ICI in combination with a VEGFR TKI). For select patients, monotherapy with either an ICI or a VEGFR TKI may be offered on the basis of comorbidities. Interleukin-2 remains an option, although selection criteria could not be identified. Recommendations are also provided for second- and subsequent-line therapy as well as the treatment of bone metastases, brain metastases, or the presence of sarcomatoid features. Participation in clinical trials is highly encouraged for patients with metastatic ccRCC.Additional information is available at www.asco.org/genitourinary-cancer-guidelines.
Pericardial Effusion Provoking Atrial Fibrillation After Cardiac Surgery
Authors: Mario Gaudino, Antonino Di Franco, Lisa Q. Rong, Davide Cao, Carlo A. Pivato, Giovanni J. Soletti, David Chadow, Gianmarco Cancelli, Roberto Perezgrovas Olaria, Marc Gillinov, J. Michael DiMaio, Leonard N. Girardi
Journal: Journal of the American College of Cardiology (2022)
Race, Genotype, and Azathioprine Discontinuation
Authors: Alyson L. Dickson, Laura L. Daniel, Elise Jackson, Jacy Zanussi, Wenjian Yang, W. Dale Plummer, William D. Dupont, Wei-Qi Wei, Puran Nepal, Adriana M. Hung, Nancy J. Cox, Sara L. Van Driest, QiPing Feng, Jun J. Yang, C. Michael Stein, Jonathan D. Mosley, Cecilia P. Chung
Journal: Annals of Internal Medicine (2022)

Thiopurines are an important class of immunosuppressants despite their risk for hematopoietic toxicity and narrow therapeutic indices. Benign neutropenia related to an
Variability of Primary Sjögren's Syndrome Is Driven by Interferon‐α and Interferon‐α Blood Levels Are Associated With the Class II HLA–DQ Locus
Authors: Diana Trutschel, Pierre Bost, Xavier Mariette, Vincent Bondet, Alba Llibre, Celine Posseme, Bruno Charbit, Christian W. Thorball, Roland Jonsson, Christopher J. Lessard, Renaud Felten, Wan Fai Ng, Lucienne Chatenoud, Hélène Dumortier, Jean Sibilia, Jacques Fellay, Karl A. Brokstad, Silke Appel, Jessica R. Tarn, Lluis Quintana‐Murci, Michael Mingueneau, Nicolas Meyer, Darragh Duffy, Benno Schwikowski, Jacques Eric Gottenberg
Journal: Arthritis & Rheumatology (2022)

Primary Sjögren's syndrome (SS) is the second most frequent systemic autoimmune disease, affecting 0.1% of the general population. To characterize the molecular and clinical variabilities among patients with primary SS, we integrated transcriptomic, proteomic, cellular, and genetic data with clinical phenotypes in a cohort of 351 patients with primary SS.We analyzed blood transcriptomes and genotypes of 351 patients with primary SS who were participants in a multicenter prospective clinical cohort. We replicated the transcriptome analysis in 3 independent cohorts (n = 462 patients). We determined circulating interferon-α (IFNα) and IFNγ protein concentrations using digital single molecular arrays (Simoa).Transcriptome analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients; this finding was replicated in the 3 independent cohorts. Because gene expression analysis did not discriminate between type I IFN and type II IFN, we used Simoa to demonstrate that the IFN transcriptomic signature was driven by circulating IFNα and not by IFNγ protein levels. IFNα protein levels, detectable in 75% of patients, were significantly associated with clinical and immunologic features of primary SS disease activity at enrollment and with increased frequency of systemic complications over the 5-year follow-up. Genetic analysis revealed a significant association between IFNα protein levels, a major histocompatibility (MHC) class II haplotype, and anti-SSA antibody. Additional cellular analysis revealed that an MHC class II HLA-DQ locus acts through up-regulation of HLA class II molecules on conventional dendritic cells.We identified the predominance of IFNα as a driver of primary SS variability, with IFNα demonstrating an association with HLA gene polymorphisms.
School racial segregation and long-term cardiovascular health among Black adults in the US: A quasi-experimental study
Authors: Min Hee Kim, Gabriel L. Schwartz, Justin S. White, M. Maria Glymour, Sean F. Reardon, Kiarri N. Kershaw, Scarlett Lin Gomez, Daniel F. Collin, Pushkar P. Inamdar, Guangyi Wang, Rita Hamad
Journal: PLoS Medicine (2022)

Background Cardiovascular disease (CVD) disproportionately affects Black adults in the United States. This is increasingly acknowledged to be due to inequitable distribution of health-promoting resources. One potential contributor is inequities in educational opportunities, although it is unclear what aspects of education are most salient. School racial segregation may affect cardiovascular health by increasing stress, constraining socioeconomic opportunities, and altering health behaviors. We investigated the association between school segregation and Black adults’ CVD risk. Methods and findings We leveraged a natural experiment created by quasi-random (i.e., arbitrary) timing of local court decisions since 1991 that released school districts from court-ordered desegregation. We used the Panel Study of Income Dynamics (PSID) (1991 to 2017), linked with district-level school segregation measures and desegregation court order status. The sample included 1,053 Black participants who ever resided in school districts that were under a court desegregation order in 1991. The exposure was mean school segregation during observed schooling years. Outcomes included several adult CVD risk factors and outcomes. We fitted standard ordinary least squares (OLS) multivariable linear regression models, then conducted instrumental variables (IV) analysis, using the proportion of schooling years spent in districts that had been released from court-ordered desegregation as an instrument. We adjusted for individual- and district-level preexposure confounders, birth year, and state fixed effects. In standard linear models, school segregation was associated with a lower probability of good self-rated health (−0.05 percentage points per SD of the segregation index; 95% CI: −0.08, −0.03; p &lt; 0.001) and a higher probability of binge drinking (0.04 percentage points; 95% CI: 0.002, 0.07; p = 0.04) and heart disease (0.01 percentage points; 95% CI: 0.002, 0.15; p = 0.007). IV analyses also found that school segregation was associated with a lower probability of good self-rated health (−0.09 percentage points; 95% CI: −0.17, −0.02, p = 0.02) and a higher probability of binge drinking (0.17 percentage points; 95% CI: 0.04, 0.30, p = 0.008). For IV estimates, only binge drinking was robust to adjustments for multiple hypothesis testing. Limitations included self-reported outcomes and potential residual confounding and exposure misclassification. Conclusions School segregation exposure in childhood may have longstanding impacts on Black adults’ cardiovascular health. Future research should replicate these analyses in larger samples and explore potential mechanisms. Given the recent rise in school segregation, this study has implications for policies and programs to address racial inequities in CVD.
Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease
Authors: Naoto Fujiwara, Naoto Kubota, Emilie Crouchet, Bhuvaneswari Koneru, Cesia A. Marquez, Arun K. Jajoriya, Gayatri Panda, Tongqi Qian, Shijia Zhu, Nicolas Goossens, Xiaochen Wang, Shuang Liang, Zhenyu Zhong, Sara Lewis, Bachir Taouli, Myron E. Schwartz, Maria Isabel Fiel, Amit G. Singal, Jorge A. Marrero, Austin J. Fobar, Neehar D. Parikh, Indu Raman, Quan-Zhen Li, Masataka Taguri, Atsushi Ono, Hiroshi Aikata, Takashi Nakahara, Hayato Nakagawa, Yuki Matsushita, Ryosuke Tateishi, Kazuhiko Koike, Masahiro Kobayashi, Takaaki Higashi, Shigeki Nakagawa, Yo-ichi Yamashita, Toru Beppu, Hideo Baba, Hiromitsu Kumada, Kazuaki Chayama, Thomas F. Baumert, Yujin Hoshida
Journal: Science Translational Medicine (2022)

Prediction of hepatocellular carcinoma (HCC) risk is an urgent unmet need in patients with nonalcoholic fatty liver disease (NAFLD). In cohorts of 409 patients with NAFLD from multiple global regions, we defined and validated hepatic transcriptome and serum secretome signatures predictive of long-term HCC risk in patients with NAFLD. A 133-gene signature, prognostic liver signature (PLS)–NAFLD, predicted incident HCC over up to 15 years of longitudinal observation. High-risk PLS-NAFLD was associated with IDO1 + dendritic cells and dysfunctional CD8 + T cells in fibrotic portal tracts along with impaired metabolic regulators. PLS-NAFLD was validated in independent cohorts of patients with NAFLD who were HCC naïve (HCC incidence rates at 15 years were 22.7 and 0% in high- and low-risk patients, respectively) or HCC experienced (de novo HCC recurrence rates at 5 years were 71.8 and 42.9% in high- and low-risk patients, respectively). PLS-NAFLD was bioinformatically translated into a four-protein secretome signature, PLSec-NAFLD, which was validated in an independent cohort of HCC-naïve patients with NAFLD and cirrhosis (HCC incidence rates at 15 years were 37.6 and 0% in high- and low-risk patients, respectively). Combination of PLSec-NAFLD with our previously defined etiology-agnostic PLSec-AFP yielded improved HCC risk stratification. PLS-NAFLD was modified by bariatric surgery, lipophilic statin, and IDO1 inhibitor, suggesting that the signature can be used for drug discovery and as a surrogate end point in HCC chemoprevention clinical trials. Collectively, PLS/PLSec-NAFLD may enable NAFLD-specific HCC risk prediction and facilitate clinical translation of NAFLD-directed HCC chemoprevention.
Integrating HIV and substance misuse services: a person-centred approach grounded in human rights
Authors: Victoria Haldane, Anne-Sophie Jung, Chuan De Foo, Pami Shrestha, Elena Urdaneta, Eva Turk, Juan I Gaviria, Jesus Boadas, Kent Buse, J Jaime Miranda, Steffanie A Strathdee, Ashley Barratt, Michel Kazatchkine, Martin McKee, Helena Legido-Quigley
Journal: The Lancet Psychiatry (2022)
CRISPR-mediated MECOM depletion retards tumor growth by reducing cancer stem cell properties in lung squamous cell carcinoma
Authors: Yuanyuan Ma, Bin Kang, Shaolei Li, Guoyun Xie, Jiwang Bi, Fuqiang Li, Guo An, Bing Liu, Jing Li, Yue Shen, Xun Xu, Huanming Yang, Yue Yang, Ying Gu, Nan Wu
Journal: Molecular Therapy (2022)

Targeted therapy for lung squamous cell carcinoma (LUSC) remains a challenge due to the lack of robust targets. Here, we identified MECOM as a candidate of therapeutic target for LUSC by screening 38 genes that were commonly amplified in three pairs of primary tumors and patient-derived xenografts (PDXs) using a clustered regularly interspaced short palindromic repeats (CRISPR)-mediated approach. High MECOM expression levels were associated with poor prognosis. Forced expression of MECOM in LUSC cell lines promoted cancer stem cell (CSC) properties, and its knockout inhibited CSC phenotypes. Furthermore, systemic delivery of CRISPR-mediated MECOM depletion cassette using adenovirus with an adaptor, which is composed of a single-chain fragment variable (scFv) against epithelial cell adhesion molecules (EpCAM) fused to the ectodomain of coxsackievirus and adenovirus receptor, and a protector, which consists of the scFv connected to the hexon symmetry of the adenovirus, could specifically target subcutaneous and orthotopic LUSC and retard tumor growth. This study could provide a novel therapeutic strategy for LUSC with high efficacy and specificity.